JP7398589B1 - External pain relief preparation containing ginger ingredients - Google Patents

Abstract

[Problem] The present invention prepares a ginger extract with low odor and skin irritation, and provides an external preparation for pain relief using the ginger extract. [Solution] The present invention is an external preparation containing 50% by weight or more of an extract obtained by extracting dried ginger (dried ginger) with vegetable oil, and is characterized by containing 10 to 200 ppm of 6-shogaol. It is an external preparation. It has little odor and skin irritation, and when used externally as a lotion or cream, it can be used particularly to alleviate neuropathic pain and cold sensations. [Selection diagram] Figure 1

Description

The present invention relates to an external preparation for pain relief containing a ginger component.

Since ancient times, ginger has been used not only as a food but also in Chinese herbal medicine as a cold medicine, digestive aid, antiemetic, and analgesic. It is well known for its antipyretic, sweating, and anti-inflammatory effects when taken internally, and is also used in cold medicines and health foods. Among these effects, the molecular biological mechanism of its anti-inflammatory effect has not been clearly defined until now, but in recent years it has been reported that 6-shogaol has the effect of protecting nerve cells from oxidative stress. (Non-Patent Document 1), the possibility of such a protective action was demonstrated. Although external preparations using ginger have been developed, they are not common and are only expected to prevent skin aging by improving blood flow and improve moisturizing function (Patent Document 1).

As with other plant-derived extracts, ginger is generally extracted using organic solvents or steam distillation. What is commonly called ginger extract is extracted from fresh or dried ginger rhizomes using a hydrophilic organic solvent such as ethanol, and then concentrated. Ginger essential oil is obtained by steam distillation of ginger rhizomes. These extracts are characterized by a very strong pungent odor. Ginger contains odorous components such as cineole and zingiberene, which are alcohol-soluble and low-boiling compounds. Therefore, the conventional extraction method has the disadvantage that these odor components are concentrated and the pungent odor inevitably becomes stronger.

On the other hand, in the process of searching for a therapeutic agent for vitiligo vulgaris, we discovered a sesame oil extract of ginger (Patent Document 2), but this extract did not have the irritating odor that conventional extracts have. The mechanism of improvement in vitiligo vulgaris is presumed to be due in part to the effect of 6-shogaol, one of the ingredients in ginger, protecting melanocytes from oxidative stress (Non-Patent Document 2). Since melanocytes and nerve cells are similar cells, we decided to investigate the idea that the effect of protecting these cells from stress could also be effective in suppressing nerve inflammation and alleviating pain. Various active ingredients such as ketoprofen and ibuprofen are known for topical pain relief, but there are still few effective topical analgesics for neuropathic pain such as postherpetic neuralgia. There are quite a few unmet needs.

JP2015-214519 JP2019-73448

Phtother. Res, Vol. 27, ISSUE 12, 2013, 1795 Int. J. Mol. Sci, Vol. 21,ISSUE10,2020,3537

The present invention creates a ginger extract with low odor and skin irritation, and provides an external preparation for pain relief using the ginger extract.

After extensive research, the present inventor discovered that by extracting dried ginger using vegetable oil, an extract with less odor and irritation can be obtained, and can be suitably used in external preparations. This is thought to be because many of the compounds that cause ginger's odor are hydrophilic and therefore difficult to extract, and the high boiling point of vegetable oils makes it difficult for odor components to diffuse through mixed steam.
The present invention was completed based on this knowledge and includes the following aspects.
Item 1. A topical preparation containing 50% by weight or more of an extract characterized by extracting dried ginger (dried ginger) powder using non-roasted sesame oil and removing the extracted dried ginger powder by filtration. Item 2. External preparation for pain relief, characterized by containing 10 to 200 ppm of 6-shogaol. The external cream according to claim 1, characterized in that it contains shea butter.

According to the present invention, a ginger component-containing external preparation with little odor can be obtained, and can be suitably used for the purpose of alleviating neuropathic pain.

FIG. 1 summarizes the components of the pain relief external preparation prepared in the examples. FIG. 2 summarizes the effects of the pain relief external preparations prepared in Examples.

1. External preparation The external preparation according to the present invention contains an extract obtained by extracting dried ginger using vegetable oil. From the viewpoint of extraction efficiency and storage stability, it is preferable to use dried ginger powder as the extraction raw material. Dried ginger powder can be easily procured from domestic Chinese herbal pharmacies.

The solvent for extraction is not particularly limited as long as it is a vegetable oil. Examples include olive oil, grapeseed oil, sesame oil, etc., and sesame oil is preferred from the viewpoint of affinity with the skin, stability in terms of quality, and solidification point. Although the sesame oil is not limited, it is preferable to use unroasted sesame oil. Since the components of roasted sesame oil are denatured by heating (approximately 150°C to 220°C) and deodorizing processes, it is preferable to select an oil that is not subjected to post-extraction treatment as much as possible.

In the present invention, the vegetable oil used is preferably heat-treated at 80 to 130° C. for about 10 to 30 minutes before performing the extraction operation. This treatment is expected to remove irritating volatile components.

The extract of the present invention is prepared by soaking dried ginger in vegetable oil, leaving it at room temperature (about 15°C to 35°C) for about 30 minutes to 24 hours, preferably about 6 to 8 hours, and then filtering it to remove solids. It can be obtained by removing the liquid layer and collecting the liquid layer. The ratio of dried ginger and vegetable oil during extraction is preferably adjusted to 10 to 100 parts by weight of vegetable oil per 1 part by weight of dried ginger.

The concentration of components extracted from dried ginger in the extract has a positive correlation with the ratio of dried ginger to vegetable oil at the time of extraction, but in general, if the ratio of solute to solvent becomes too large, Since the proportion remaining on the solute side increases, the extraction efficiency decreases. If the above quantitative ratio is too small, the amount of ingredients extracted will be too small and the concentration of the active ingredient will be diluted, and if it is too large, the extraction efficiency will decrease and the effective ingredient will not be extracted as much, so the quantitative ratio should be 1:10 to 100. It is preferable to set it as approximately.

Since it is technically difficult to control all extracted components, it is preferable to control the compound concentration, which is an indicator of effectiveness, as a representative value. When using 6-shogaol as a representative value as an indicator of the concentration in the extract, the concentration is preferably 10 ppm or more and 200 ppm or less. The concentration of 6-shogaol depends on the amount contained in dried ginger, which is the raw material, and the ratio of the amount to the vegetable oil at the time of extraction, so it is necessary to manage each raw material. Furthermore, in the extraction method of the present invention, there is an upper limit to the concentration of 6-shogaol contained in the extract because it is technically difficult to concentrate by evaporating the solvent. After conducting a study with reference to the experimentally determined distribution coefficient of 6-shogaol between dried ginger and common vegetable oils and literature values for 6-shogaol contained in dried ginger, the extraction method of the present invention was found. It was technically difficult to extract more than 200 ppm of 6-shogaol.

As mentioned above, 6-shogaol has been reported to have the effect of protecting nerve cells from disorders such as oxidative stress, and it has been reported that 6-shogaol has the effect of protecting nerve cells from damage such as oxidative stress, and can cause damage to nerve cells themselves and related cells, such as in postherpetic neuralgia and arthralgia. It is expected to reduce stress on nerve tissue caused by inflammation and alleviate pain. Within the above concentration range, pain relief effects can be obtained although there are individual differences.

For example, it is possible to obtain a similar composition by mixing an alcoholic extract or essential oil containing 6-shogaol with a carrier such as vegetable oil or ethanol, but these extracts and essential oils contain odor components. Since it contains many irritating ingredients including , the composition becomes extremely irritating to the skin and cannot be put to practical use. For this reason, the external preparation of the present invention is obtained by directly extracting dried ginger with vegetable oil.

The external preparation of the present invention can be prepared by using the above-mentioned extract without diluting or by mixing the above-mentioned extract with the following base material. The dosage forms of the external preparation of the present invention include creams and liquid preparations. Preferably it is an oily cream.

The base raw material is preferably hydrophobic. In the external preparation of the present invention, sesame oil is expected to promote the penetration of the active ingredient into the skin. It is also expected that the hydrophobic base will allow the active ingredient to more easily pass through the skin's barrier function. Therefore, in order not to interfere with these effects, it is preferable that the external preparation of the present invention does not contain excess water or a surfactant that emulsifies the water and the hydrophobic base material.

The base raw material for the external preparation of the present invention is not particularly limited as long as it is used for preparing pharmaceuticals, quasi-drugs, and cosmetics.

Base raw materials include oils and fats (avocado oil, camellia oil, rice bran oil, safflower oil, soybean oil, corn oil, rapeseed oil, apricot kernel oil, persic oil, sunflower oil, peach kernel oil, cottonseed oil, coconut oil, Wheat germ oil, rice germ oil, evening primrose oil, hybrid sunflower oil, macadamia nut oil, meadow farm oil, hazelnut oil, olive oil, castor oil, sesame oil, almond oil, grapeseed oil, shea butter, palm kernel oil, palm oil, coconut Oil, cacao butter, wood wax, argan oil, rosehip oil, mink oil, turtle oil, egg yolk oil, beef tallow, milk fat, lard, horse oil, etc.), hydrocarbons (vegetable squalene, vegetable squalane, petrolatum, Microcrystalline petrolatum, squalene, squalane, liquid paraffin, paraffin, soft isoparaffin, liquid isoparaffin, liquid polyisobutylene, hydrogenated polyisobutylene, ozokerite, ceresin, synthetic squalane, α-olefin oligomer, polybutene, polyethylene, etc.), fatty acid esters ( Isopropyl myristate, isopropyl palmitate, butyl stearate, ethyl oleate, cetyl palmitate, myristyl myristate, octyldodecyl mystilate, octyldodecyl oleate, cholesteryl stearate, cholesteryl hydroxystearate, tricaprylin, trimyristin, trio Cutanoin, isopropyl isostearate, ethyl isostearate, cetyl ethylhexanoate, stearyl ethylhexanoate, glyceryl triethylhexanoate, trimethylolpropane triethylhexanoate, etc., pentaerythrityl tetraethylhexanoate, glyceryl triisostearate, triisostearate Methylolpropane, pentaerythrityl tetraisostearate, isocetyl isostearate, octyldodecyl dimethyloctanoate, myristyl lactate, cetyl lactate, trioctyldodecyl citrate, diisostearyl malate, etc.), waxes (beeswax, lanolin, reduced lanolin, Jojoba oil, carnauba wax, candelilla wax, rice bran wax, orange roughy oil, shellac, montan wax, etc.), higher fatty acids (lauric acid, stearic acid, myristic acid, palmitic acid, behenic acid, oleic acid, linoleic acid, ethylhexanoic acid, isostearic acid, isopalmitic acid, isotridecanoic acid, isononanoic acid, pentadecanoic acid, etc.), higher alcohols (lauryl alcohol, stearyl alcohol, cetearyl alcohol, behenyl alcohol, oleyl alcohol, lanolin alcohol, cetanol, cholesterol, isocholesterol, sitosterol, stigma) sterol, isostearyl alcohol, octyldodecanol, hexyldecanol, etc.), silicone oil, etc.

Preferred base materials include oils and fats (avocado oil, camellia oil, rice bran oil, macadamia nut oil, hazelnut oil, olive oil, castor oil, sesame oil, almond oil, grapeseed oil, shea butter, palm kernel oil, palm oil, coconut oil). oil, cacao butter, wood wax, argan oil, rosehip oil), hydrocarbons (vegetable squalene, vegetable squalane, petrolatum, microcrystalline petrolatum, squalene, squalane, synthetic squalane), and waxes (beeswax, lanolin, The wax is at least one selected from the group consisting of reduced lanolin, jojoba oil, carnauba wax, candelilla wax, and rice bran wax. More preferred base materials include sesame oil, sweet almond oil, vegetable squalane, squalane, vaseline, beeswax, shea butter, and jojoba oil. More preferred as the base raw material is shea butter. Since the softening point of shea butter is close to body temperature, the mixture blends well with the skin and is suitable.

When the extract is diluted with a base raw material, the content of the extract may be in the range of 50 to 80% by weight when the total amount of the external preparation is 100% by weight. The purpose of dilution is to increase the viscosity to make it creamy, and by including 20 to 50% by weight of solid ingredients such as shea butter and beeswax, it is possible to adjust the desired viscosity and softening point of the external preparation. It becomes possible.

Since the external preparation of the present invention is based on vegetable oil, it preferably contains a vitamin E compound, which is an antioxidant. Examples of the vitamin E compound include tocopherol, tocopherol acetate, tocopherin, and tocopherin acetate. The content of the vitamin E compound may be within the range of 0.01 to 5% by weight when the total amount of the external preparation is 100% by weight.

The external preparation of the present invention includes plant extracts other than ginger (essential oils, infused oils, dry extracts, etc.) that have anti-inflammatory effects, antibacterial effects, antifungal effects, wound healing effects, skin roughness prevention effects, sebum secretion suppressing effects, etc. It may also contain additives such as bactericides, preservatives, and antioxidants.

Plant extracts other than dried ginger include calendula extract (flower essential oil, infused oil, tincture, extract, etc.), arnica extract (flower infused oil, etc.), sage extract (leaf essential oil, infused oil, tincture, etc.) , extract, etc.), rosemary extract (leaf essential oil, infused oil, tincture, extract, etc.), tea tree extract (leaf essential oil, etc.), neem extract (neem oil squeezed from the core of the fruit using a press) , Burdock extract (root infusion oil, extract, etc.), Eucalyptus extract (leaf essential oil, etc.), Lavender extract (flower essential oil, tincture, extract, aromatic distilled water, etc.), Lemon balm extract (leaf essential oil, etc.) ), Heutyami extract (leaf tincture, extract, etc.), Coix barley extract (fruit extract, tincture, etc.), Heath extract (flower extract, tincture, etc.), Exeana extract (whole plant tincture, extract, etc.) , Malva extract (flower or leaf extract, tincture, etc.), German chamomile (flower essential oil extract, tincture, extract, etc.), Marshmallow extract (root or leaf extract, etc.), Yarrow extract (flower essential oil) , extract, tincture, etc.). Preferred are calendula extract (particularly calendula oil), tea tree extract (leaf essential oil), Houtyami extract (particularly leaf tincture, extract), and adlay extract (fruit extract, tincture, etc.), and particularly preferred are It's calendula oil. For the purpose of adjusting the active ingredient concentration, it is possible to add a small amount of ginger extract.

These plant extracts may be prepared according to known methods, and can be purchased from Tree of Life Co., Ltd., Naturas Psychos (Herbal Index Co., Ltd.), Neal's Yard Remedies Co., Ltd., and the like.

As disinfectants or preservatives, benzoic acid, dehydroacetic acid, phenylethanol, phenoxyisopropyl alcohol, hydroxybenzoic acid esters, chlorcresol, benzalkonium chloride, benzethonium chloride, chlorhexidine, propylene glycol, paraoxybenzoic acid ester, sorbitic acid , thymol and the like.

Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, arbutin, kojic acid, ellagic acid, rucinol, vitamin C and its derivatives, linoleic acid, and the like.

When the extract is a dried extract, the content of plant extracts other than dried ginger is in the range of 0.001 to 5% by weight, when the total amount of the external preparation is 100% by weight. The lower limit of the content of the dry extract is preferably 0.01% by weight, more preferably 0.05% by weight. The upper limit of the content of the dry extract is preferably 2% by weight, more preferably 1% by weight.

If the plant extract other than dried ginger is infused oil, it is sufficient that the plant extract is contained in a range of 5 to 50 volumes when the total volume of the external preparation is 100 volumes, and the content depends on the dosage form. It can be prepared within a range that can maintain its shape. The lower limit of the content of the vegetable infused oil is preferably 20 volumes. The upper limit of the content of the plant extract is preferably 50 volumes.

If the plant extract other than dried ginger is an essential oil, it is sufficient that the plant extract is contained in the range of 0.01 to 1 volume when the total volume of the external preparation is 100 volumes; It can be prepared within a range that can maintain its shape. The lower limit of the content of the vegetable infused oil is preferably 0.1 volume. The upper limit of the content of the plant extract is preferably 0.3 volume.

In addition, additives include ultraviolet absorbers (para-aminobenzoic acid and its derivatives, cinnamic acid and its derivatives, benzophenone and its derivatives, salicylic acid and its derivatives, etc.), ultraviolet scattering agents (titanium oxide, zinc oxide, etc.), It may contain ingredients (collagen, hyaluronic acid, ceramide, hormones, placenta extract, etc.).

In addition, the external preparation of the present invention may include colorants and fragrances (essential oils such as rose, geranium, lavender, peppermint, lemon, neroli, grapefruit, orange, etc.), pH regulators (phosphoric acid, citric acid, (sodium citrate, lactic acid, diisopropanolamine, acetic acid, sodium acetate, succinic acid, sodium succinate, malic acid, sodium malate, etc.) may be added.

Additives such as bactericides, preservatives, antioxidants, ultraviolet absorbers, and biological components can be added as appropriate in the range of 0.00001 to 10% by weight of the external preparation.
The content of each raw material contained in the base of each dosage form can be appropriately set within a range that maintains the dosage form to be prepared.

2. Method for Preparing External Preparation The external preparation of the present invention can be prepared by known methods. For example, heat the extract of the present invention at about 60 to 80°C, add the above raw materials or other extracts, mix for about 5 to 10 minutes, add additives such as vitamin E compound and essential oil, and stir. A liquid preparation can be obtained by filtering out insoluble matters. If a high melting point base material such as beeswax is added, it is possible to prepare an external composition in the form of a cream or the like after cooling.

3. Application of external preparation and treatment method The external preparation of the present invention can be used as a pharmaceutical, a quasi-drug, or a cosmetic. Here, cosmetics include medicated cosmetics (cosmetics containing active ingredients) defined in the "Act on Assuring the Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, etc."

The external preparation of the present invention is expected to alleviate pain due to the nerve cell protective effect of the ingredients contained in ginger, and maintain moisturizing and skin functions due to the effects of increasing heat generation, sweating, and blood flow.

Examples of the present invention will be shown below, but the present invention is not limited to the following examples.

Preparation of external preparations External preparations were formulated according to Examples 1 to 4 and Comparative Examples 1 to 2 described below. The dried ginger used was purchased from a Chinese herbal medicine pharmacy, and the sesame oil used was purchased from Summit Essential Oil Co., Ltd. Tocopherol and various essential oils were purchased from commercially available raw materials for cosmetics.

Example 1
100 g of sesame oil was preheated at 80° C. for 30 minutes. Thereafter, the heating was stopped, 1 g of dried ginger powder was added, and the mixture was left to cool naturally for 24 hours. 0.3 g of tocopherol was added to the obtained extract and stirred at room temperature for 10 minutes to dissolve. After dissolution, the raffinate residue was removed using a filter capable of cutting particles of 1 μm to obtain external preparation 1. The content of ginger-derived components in the obtained external preparation 1 was analyzed by high-performance liquid chromatography at the Japan Food Research Institute. As a result, the concentration of 6-shogaol was 17 ppm.

Example 2
100 g of sesame oil was preheated at 80° C. for 30 minutes. Thereafter, the heating was stopped, 10 g of dried ginger powder was added, and the mixture was left to cool naturally for 24 hours. To this extract, 0.3 g of tocopherol was added and stirred at room temperature for 10 minutes to dissolve. After dissolution, the raffinate residue was removed using a filter capable of cutting particles of 1 μm to obtain external preparation 2. The concentration of 6-shogaol in the obtained external preparation 2 was 77 ppm.

Example 3
100 g of sesame oil was preheated at 80° C. for 30 minutes. Thereafter, the heating was stopped, 3 g of dried ginger powder was added, and the mixture was left to cool naturally for 24 hours. To this extract, 0.3 g of tocopherol was added and stirred at room temperature for 10 minutes to dissolve. After dissolution, the raffinate residue was removed using a filter capable of cutting particles of 1 μm to obtain external preparation 3. The concentration of 6-shogaol in the obtained external preparation 3 was 35 ppm.

Example 4
Put 100 g of the external preparation 2 obtained in Example 3 into a glass container, add 15 g of shea butter and 15 g of beeswax, heat and stir at 70°C for about 10 minutes to completely dissolve the shea butter and beeswax, then cool. A cream-like external preparation 4 was obtained. The concentration of 6-shogaol in the obtained external preparation 4 was 60 ppm.

Comparative example 1
100 g of sesame oil was preheated at 80° C. for 30 minutes. Comparative agent 1 was prepared by adding 0.1 g of commercially available ginger essential oil (manufactured by Incent Co., Ltd.).

Comparative example 2
100 g of sesame oil was preheated at 80° C. for 30 minutes. Comparative agent 2 was prepared by adding 0.5 g of commercially available ginger essential oil (manufactured by Incent Co., Ltd.).

The composition of each external composition is shown in FIG.

Evaluation method

Five volunteers were asked to apply the topical preparations of Examples 1 to 5 and Comparative Examples 1 to 2 on the painful area, and a questionnaire was conducted regarding whether they felt warm (warm sensation), pain relief effects, and whether there was an odor after use. I did it. As a result, for Example 1, 3 out of 5 people answered that they felt it was effective, and 2 people answered that they felt no effect. Regarding Examples 2 to 5, all respondents answered that they felt the effects. Regarding the odor after use, for all Examples 1 to 5, respondents answered that there was no odor or that it did not bother them. On the other hand, for Comparative Examples 1 and 2, all respondents answered that they did not feel any effect and that there was a strong irritating odor after use.

The results of the evaluation are shown in Figure 2.

Regarding the results of this evaluation, although it is difficult to attribute the effect to a single ingredient, the inventors believe that 6-shogaol is one of the active ingredients. Therefore, the concentration of 6-shogaol is controlled during extraction. The extraction method of the present invention is characterized by a relatively small amount of components that cause irritating odors, and perhaps because of this, there were no side reactions during external use and the odor was at a level that was not bothersome. Because it has little odor, the odor of external preparations can be adjusted by adding other essential oils. In addition, the effect was immediate, probably because the base material is lipophilic and penetrates into the skin quickly.

Claims (2)

A topical preparation containing 50% by weight or more of an extract characterized by extracting dried ginger (dried ginger) powder using non-roasted sesame oil and removing the extracted dried ginger powder by filtration. , an external preparation for pain relief characterized by containing 10 to 200 ppm of 6-shogaol
The external cream according to claim 1, characterized in that it contains shea butter.

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